Induced
pluripotent
stem or IPS cells as regenerative therapy may be
overrated, said Ian Wilmut, who led the team that cloned Dolly the
sheep in 1996. Newer approaches that bypass the stem-cell stage
promise to directly create needed replacement cells, Wilmut said at
the recent Stem Cell Meeting on the Mesa at the Salk Institute,
held Nov. 30-Dec. 1.

The IPS stem cells are adult cells that have been genetically
reprogrammed so that they have properties similar to embryonic stem
cells.

A video of part of Wilmut's speech is presented with this blog
post, edited to focus on the portions pertaining to IPS and direct
cell transformation technologies. I'm giving a synopsis of Wilmut's
talk here, along with some explanation for those not knowledgeable
about this subject. I've included links to articles that provide
more information.

The video clip opens with Wilmut referring to
Shinya Yamanaka
, the Japanese scientist whose team was
the first
to make human IPS cells
. These cells act much like embryonic
stem cells, but can be created from adult skin cells. They thus
avoid the ethical issue many have with developing therapies made
from human embryos.

In addition, IPS cells hold the potential for personalized
therapy. A patient with a damaged spinal cord, for example, could
receive a transplant of new spinal cord tissue, grown from his own
cells. Likewise, a patient with Parkinson's disease could receive
new dopamine-producing brain cells. (In the case of inherited
disease, researchers are investigating whether these cells could be
corrected with
gene therapy
before being transplanted back into patients).

Wilmut said the IPS approach shares a major disadvantage with
embryonic stem cells in that such cells are prone to form tumors.
Direct cell transformation avoids that pitfall, he said.

As befits their pluripotent status, IPS cells can grow into
nearly any type of cell in the body. But the technology to control
their transformation is inexact. When millions of cells are being
grown from IPS cells into the desired type, some inevitably fail to
transform. And in the early stages, others transform unpredictably
into a mixture of types, creating what Wilmut called "a zoo of
cells."

If even a few of the untransformed IPS cells are transplanted
into a patient, they can produce tumors as they spontaneously
change into various types of cells located where they don't belong.
That means transplanted cells must be tested to a very high level
of purity to make them safe for transplantation.

But recent research has shown it is possible to directly
transform cells of one type into cells of another type, avoiding
the tricky pluripotent stage altogether, Wilmut said. This research
is still in its early stage, he said, but merits much more study to
find out whether it can become practical.

Wilmut gave a few caveats:

He is not denying that IPS cells represent a great advance in
stem cell research that deserves study.

The first medical uses of IPS cells are likely to be in testing
drugs for toxicity, not for therapy.

Patients shouldn't expect direct transformation cell therapy to
become available for perhaps a decade or more.

"I think that there's a balance there," Wilmut said. "We should
be excited by this possibility, we should work towards it, but we
do have to be realistic when we're talking to people who might
depend on this. It will take 10 to 20 years at least before it gets
into routine therapy."